BACKGROUND AND AIMS: Gastrokine 1 (GKN1) is a stomach-specific protein that is normally expressed in gastric mucosa but not in primary tumours and cell lines. Based on this evidence, it was presumed that GKN1 might play a role in gastric cancer development; however, its function and molecular mechanism are not clear. A systematic study was initiated that combined multiple approaches to define the molecular mechanism of GKN1 in gastric cancer cells. METHOD: Proteomics, western blotting and immunohistochemistry were used to measure the expression level of GKN1. Western blotting combined with immunofluorescence was used to monitor the secretory process of this protein. Subsequently, the function and molecular mechanism of GKN1 was explored in vitro and in vivo. RESULTS: It was shown that GKN1 is an autocrine/paracrine protein and inhibits cell growth due to senescence, which resulted from activation of p16/Rb and p21(waf) pathways. Furthermore, sustained activation of Ras/Raf/MEK/ERK signalling was characterised in gastric cancer cells and a xenograft nude mouse model following GKN1 treatment. CONCLUSION: These results provide comprehensive molecular evidence of GKN1 in inducing senescence of gastric cancer cells, and indicate that GKN1 might be a potential novel target for gastric cancer therapeutics.
BACKGROUND AND AIMS: Gastrokine 1 (GKN1) is a stomach-specific protein that is normally expressed in gastric mucosa but not in primary tumours and cell lines. Based on this evidence, it was presumed that GKN1 might play a role in gastric cancer development; however, its function and molecular mechanism are not clear. A systematic study was initiated that combined multiple approaches to define the molecular mechanism of GKN1 in gastric cancer cells. METHOD: Proteomics, western blotting and immunohistochemistry were used to measure the expression level of GKN1. Western blotting combined with immunofluorescence was used to monitor the secretory process of this protein. Subsequently, the function and molecular mechanism of GKN1 was explored in vitro and in vivo. RESULTS: It was shown that GKN1 is an autocrine/paracrine protein and inhibits cell growth due to senescence, which resulted from activation of p16/Rb and p21(waf) pathways. Furthermore, sustained activation of Ras/Raf/MEK/ERK signalling was characterised in gastric cancer cells and a xenograft nude mouse model following GKN1 treatment. CONCLUSION: These results provide comprehensive molecular evidence of GKN1 in inducing senescence of gastric cancer cells, and indicate that GKN1 might be a potential novel target for gastric cancer therapeutics.
Authors: Jung Hwan Yoon; In-Hye Ham; Olga Kim; Hassan Ashktorab; Duane T Smoot; Suk Woo Nam; Jung Young Lee; Hoon Hur; Won Sang Park Journal: Gastric Cancer Date: 2018-04-27 Impact factor: 7.370
Authors: Olga Kim; Jung Hwan Yoon; Won Suk Choi; Hassan Ashktorab; Duane T Smoot; Suk Woo Nam; Jung Young Lee; Won Sang Park Journal: Gastric Cancer Date: 2015-03-10 Impact factor: 7.370
Authors: Jung Hwan Yoon; Young Hwi Kang; Yoo Jin Choi; In Soo Park; Suk Woo Nam; Jung Young Lee; Yun Sil Lee; Won Sang Park Journal: J Cancer Res Clin Oncol Date: 2011-09-07 Impact factor: 4.553
Authors: Jung Hwan Yoon; Mi La Cho; Yoo Jin Choi; Ji Yeon Back; Mi Kyung Park; Suk Woo Lee; Byung Joon Choi; Hassan Ashktorab; Duane T Smoot; Suk Woo Nam; Jung Young Lee; Won Sang Park Journal: J Cell Biochem Date: 2013-08 Impact factor: 4.429
Authors: Marwa Matboli; Sarah El-Nakeep; Nourhan Hossam; Alaa Habieb; Ahmed E M Azazy; Ali E Ebrahim; Ziad Nagy; Omar Abdel-Rahman Journal: World J Gastroenterol Date: 2016-07-14 Impact factor: 5.742
Authors: R Xing; L Li; L Chen; Z Gao; H Wang; W Li; J Cui; G Tian; Q Liang; J Yu; J J Sung; G Luo; H Gao; X Xu; H Yang; J Wang; X Zhang; J M Wang; J Huang; Y Yu; J Wang; Y Lu Journal: Oncogene Date: 2015-09-14 Impact factor: 9.867